As is well known in the art, delivery of pharmacological agents (or drugs) to a specific organ or tissue can be achieved through systemic or local administration. In systemic administration, the agent is introduced into the systemic, or general, circulation by ingestion, injection, inhalation or transdermal administration. Circulating blood delivers the agent to the target tissue by either passive or active transport.
Advantages of systemic administration are that this mode of administration, especially by ingestion, is simple and well accepted by the patient. A disadvantage, however, is that the agent must be administered at relatively high doses in order to reach the target area in sufficient quantity. Moreover, the agent is delivered to the entire body, which can include sites where the agent can cause significant side effects. This is especially true for chemotherapeutic agents that tend to present significant systemic toxicity, and steroids, which present significant long-term systemic side effects.
Another significant disadvantage of systemic administration is that transfer of many pharmacological agents from the blood to certain tissues, such as the brain or an eye, is very inefficient.
An alternative to systemic administration is to administer the pharmacological agent(s) into a target organ (or tissue) or in close proximity thereto. However, as is well known in the art, local administration of an agent into or proximate an organ; particularly, an eye, typically requires strict adherence to numerous safeguards.
As discussed in detail herein, the eye is a delicate sensory organ that is surrounded by specialized structures and protected by the orbit bones, soft tissues and eyelids. The eye itself is composed of three primary layers: the sclera, the uvea, and the retina. The iris, ciliary body and choroid constitute the uvea.
Blood is transmitted through the choroid and the central retinal artery to the retina. The intraocular pressure (IOP) therein is normally below approximately 20 mm Hg. As is well known in the art, significant elevation of the IOP can, and in many instances will, collapse the choroidal and, subsequently, the retinal circulation. A long standing pressure rise can also cause rapid blindness.
Because of the complex nature of the eye, it is susceptible to a large number of abnormalities (and/or diseases). The abnormalities include dry eye, allergies, infections, various inflammatory diseases and glaucoma.
Treatments of the abnormalities and diseases have, in general, been limited to topical administration of agents or preparations. A conventional example of topical administration of an agent to the eye is the delivery of timolol via eye drops.
As is well known in the art, eye drops facilitate transmission of the agent directly to the anterior part of the eye by instillation into the cul-de-sac. The agents are then moved via the tears of the eye across the cornea and sclera into the anterior and posterior chambers of the eye without initially entering the systemic circulation path.
The advantage of this mode of administration (or delivery) is that the agent is concentrated in the target tissue with a much lower systemic exposure. This tends to reduce the above-mentioned systemic effects.
A disadvantage of this mode of administration is that not all eye tissues are accessible by this route of delivery. Tears can also redirect a significant portion of the agent away from the target area relatively quickly.
A further disadvantage of this mode of administration is that it is mostly applicable to small molecular weight pharmacological agents. Indeed, large molecular weight agents, such as antibodies, are known to diffuse poorly across the cornea or the sclera.
More recently, intravitreal injection methods and systems have been employed to administer pharmacological agents to the eye to abate abnormalities, such as macular degeneration, diabetic retinopathy and posterior uveitis. The noted agents include steroids, for which long-term systemic side effects are significant, as well as antibodies, which are known to diffuse poorly from the blood into the eye tissues.
Illustrative are the intravitreal injection methods and systems disclosed in U.S. Pat. Pub. Nos. 2003/0060763 A1 and 20070005016 A1. In U.S. Pat. Pub. No. 2003/0060763 an intravitreal injection method and system is disclosed having a plaque containing guide means for location of a needle entry point into the eye, which thereby facilitates such injection. According to the disclosure, the plaque conforms generally to the shape of the cornea and is maintained in place on the eye via contact with the eyelids. Injection occurs though a guide within the plaque via a conventional needle and syringe.
In U.S. Pat. Pub. No. 2007/0005016 another intravitreal injection method and device is disclosed that is adapted to perform injection of an agent formulation into the pars plana portion of the eye using a conventional needle and syringe. The noted publication does not, however, disclose any means of safely securing the device to the eye during injection of the agent formulation.
Although the noted intravitreal injection methods and systems represent an improvement over conventional injection with a needle and/or syringe, there are several disadvantages and shortcomings associated therewith. A major drawback is that the methods and systems disclosed in the noted references, as well as known prior art intravitreal injection methods and systems, do not provide means to properly secure the plate or the frame on the eye.
The noted intravitreal injection methods and systems also require a number of steps following the placement of the device on the surface of the eye. Further, and most importantly, the prior art intravitreal injection methods and systems employ conventional syringes and needles, which require complete penetration of the sclera and manual, non automatic, injection.
Even more recently, intraocular injection using needleless jet injection has been employed to administer pharmacological agents to the eye. Illustrative are the methods and systems disclosed in U.S. Pat. Pub. Nos. 2007/0052139, 2007/0055199, 2007/0055200 and 2007/0055214. There are, however, similarly several disadvantages and drawbacks associate with the disclosed methods and systems. A major disadvantage is that they do not include a transfer mechanism for safe, accurate, consistent, and fast injection of pharmacological agents into the intravitreal compartment of the eye.
Associated with the development of new pharmacological treatments for retinal diseases, vitreoretinal specialists are being faced with the responsibility for providing an ever increasing number of intravitreal injections of pharmacological agents and, hence, addressing the aforementioned issues associated with the prior art intravitreal injection methods and systems. There is also no universally accepted standard process for performing an intravitreal injection.
Further, intravitreal injections cannot always be scheduled in advance and each injection requires several steps to prepare the eye and safely perform the injection. The time required to perform injections can thus disrupt office schedules, resulting in unexpected prolongation of patient waiting times.
Therefore, a method and device to standardize and simplify the intravitreal injection process, improve patient comfort and safety, and increase efficiency of the process is desired.
It is therefore an object of the present invention to provide an intravitreal injection method and system that provides safe, accurate, consistent, and rapid injection of therapeutic agents into the intravitreal compartment of the eye.
It is another object of the present invention to provide an intravitreal injection method and system that facilitates injection of therapeutic agents into the intravitreal compartment of the eye with minimal risk of trauma to the patients' eye by the delivery system.
It is another object of the present invention to provide an intravitreal injection method and system that facilitates injection of therapeutic agents into the intravitreal compartment of the eye with minimal risk of trauma produced by jet formation inside the eye.
It is another object of the present invention to provide an intravitreal injection method and system that facilitates injection of agents into the subconjunctival, subtenon spaces or intrascleral and subchoroidal space.
It is another object of the present invention to provide an intravitreal injection method and system that facilitates injection of therapeutic agents into the intravitreal compartment of the eye with minimal risk of infection to the patient.
It is another object of the present invention to provide an intravitreal injection method and system that provides semi-automated injection of therapeutic agents into the intravitreal compartment of the eye.